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CRAC channels as targets for immunotherapy

Kenneth Stauderman1, Sudarshan Hebbar1, Stefan Feske2

  • 1CalciMedica Inc., La Jolla, CA 92037, USA.

Current Opinion in Immunology
|April 23, 2026
PubMed

Insights

Calcium release-activated calcium (CRAC) channels are vital for immune cell function and linked to immune disorders. Inhibiting these channels shows promise for treating inflammatory conditions.

Area of Science:

  • Immunology
  • Cell Biology
  • Pharmacology

Background:

  • Calcium release-activated calcium (CRAC) channels regulate store-operated calcium entry in immune and non-immune cells.
  • CRAC channels are critical for immune cell function and implicated in immune-related disorders.
  • Mutations in ORAI1 and STIM1 genes, encoding CRAC channel components, cause inborn errors of immunity.

Purpose of the Study:

  • To provide an overview of CRAC channels in immune cell function.
  • To review the role of CRAC channels in preclinical models of immune diseases.
  • To discuss the outcomes of clinical trials involving CRAC channel inhibitors (CRACi).

Main Methods:

  • Review of existing literature on CRAC channel function in immunity.
  • Analysis of preclinical studies using knockout mice and CRAC inhibitors.
  • Examination of clinical trial data for CRAC inhibitors in inflammatory disorders.

Main Results:

  • CRAC channels are essential for the function of various immune cell types.
  • Preclinical studies confirm CRAC channel involvement in infection immunity, autoimmunity, allergy, and inflammation.
  • Clinical trials suggest CRAC inhibitors have potential as immunotherapies for inflammatory diseases.

Conclusions:

  • CRAC channels play a fundamental role in immune responses and disease pathogenesis.
  • CRAC inhibitors represent a promising therapeutic strategy for immune-related and inflammatory conditions.
  • Further clinical investigation of CRAC inhibitors is warranted for immunotherapy.

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